Importance: Immune dysregulation contributes to poorer outcomes in COVID-19. Objective: To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia. Design, setting, and participants: Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia. The results of 3 substudies are reported from 95 hospitals at 85 clinical research sites in the US and Latin America. Hospitalized patients 18 years or older with confirmed SARS-CoV-2 infection within 14 days and evidence of pulmonary involvement underwent randomization between October 2020 and December 2021. Interventions: Single infusion of abatacept (10 mg/kg; maximum dose, 1000 mg) or infliximab (5 mg/kg) or a 28-day oral course of cenicriviroc (300-mg loading dose followed by 150 mg twice per day). Main outcomes and measures: The primary outcome was time to recovery by day 28 evaluated using an 8-point ordinal scale (higher scores indicate better health). Recovery was defined as the first day the participant scored at least 6 on the ordinal scale. Results: Of the 1971 participants randomized across the 3 substudies, the mean (SD) age was 54.8 (14.6) years and 1218 (61.8%) were men. The primary end point of time to recovery from COVID-19 pneumonia was not significantly different for abatacept (recovery rate ratio [RRR], 1.12 [95% CI, 0.98-1.28]; P = .09), cenicriviroc (RRR, 1.01 [95% CI, 0.86-1.18]; P = .94), or infliximab (RRR, 1.12 [95% CI, 0.99-1.28]; P = .08) compared with placebo. All-cause 28-day mortality was 11.0% for abatacept vs 15.1% for placebo (odds ratio [OR], 0.62 [95% CI, 0.41-0.94]), 13.8% for cenicriviroc vs 11.9% for placebo (OR, 1.18 [95% CI 0.72-1.94]), and 10.1% for infliximab vs 14.5% for placebo (OR, 0.59 [95% CI, 0.39-0.90]). Safety outcomes were comparable between active treatment and placebo, including secondary infections, in all 3 substudies. Conclusions and relevance: Time to recovery from COVID-19 pneumonia among hospitalized participants was not significantly different for abatacept, cenicriviroc, or infliximab vs placebo. Trial registration: ClinicalTrials.gov Identifier: NCT04593940.

Background: The performance of rapid antigen tests (Ag-RDTs) for screening asymptomatic and symptomatic persons for SARS-CoV-2 is not well established. Objective: To evaluate the performance of Ag-RDTs for detection of SARS-CoV-2 among symptomatic and asymptomatic participants. Design: This prospective cohort study enrolled participants between October 2021 and January 2022. Participants completed Ag-RDTs and reverse transcriptase polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 every 48 hours for 15 days. Setting: Participants were enrolled digitally throughout the mainland United States. They self-collected anterior nasal swabs for Ag-RDTs and RT-PCR testing. Nasal swabs for RT-PCR were shipped to a central laboratory, whereas Ag-RDTs were done at home. Participants: Of 7361 participants in the study, 5353 who were asymptomatic and negative for SARS-CoV-2 on study day 1 were eligible. In total, 154 participants had at least 1 positive RT-PCR result. Measurements: The sensitivity of Ag-RDTs was measured on the basis of testing once (same-day), twice (after 48 hours), and thrice (after a total of 96 hours). The analysis was repeated for different days past index PCR positivity (DPIPPs) to approximate real-world scenarios where testing initiation may not always coincide with DPIPP 0. Results were stratified by symptom status. Results: Among 154 participants who tested positive for SARS-CoV-2, 97 were asymptomatic and 57 had symptoms at infection onset. Serial testing with Ag-RDTs twice 48 hours apart resulted in an aggregated sensitivity of 93.4% (95% CI, 90.4% to 95.9%) among symptomatic participants on DPIPPs 0 to 6. When singleton positive results were excluded, the aggregated sensitivity on DPIPPs 0 to 6 for 2-time serial testing among asymptomatic participants was lower at 62.7% (CI, 57.0% to 70.5%), but it improved to 79.0% (CI, 70.1% to 87.4%) with testing 3 times at 48-hour intervals. Limitation: Participants tested every 48 hours; therefore, these data cannot support conclusions about serial testing intervals shorter than 48 hours. Conclusion: The performance of Ag-RDTs was optimized when asymptomatic participants tested 3 times at 48-hour intervals and when symptomatic participants tested 2 times separated by 48 hours. Primary funding source: National Institutes of Health RADx Tech program.

Rises in parental vaccine hesitancy, observed during the COVID-19 pandemic, threaten public health. This is especially concerning for vaccines not typically required for school-entry, such as the vaccines for COVID-19 and human papillomavirus (HPV), both of which also have much lower rates of completion compared to other adolescent vaccines. Pediatricians are well-positioned to address vaccine hesitancy and can offer insights into parents' perspectives in this area. There is evidence that pediatricians' sharing their own vaccine stories may help to address parents' concerns; yet we have little information on pediatricians' or their children's COVID-19 vaccine uptake. To address these gaps, we conducted a cross-sectional survey about Massachusetts pediatricians' behaviors and perspectives on vaccines that face significant resistance: HPV and COVID-19 vaccines. A total of 144 people initiated the survey, and 109 participants were eligible and completed the survey. Participants reported high levels of COVID-19 vaccine uptake for themselves (97%) and their children (98%). Similarities in parents' resistance toward both vaccines were identified: fear of side effects; general vaccine resistance. Pediatricians reported a rise in vaccine hesitancy since the beginning of the COVID-19 pandemic. Future research should focus on identifying strategies to build overall vaccine confidence and streamline these efforts for pediatricians.

Background: The first wave of the COVID-19 pandemic was associated with restricted access to reproductive care including delayed abortion and female sterilization procedures, in addition to altered maternity care experiences. Given high rates of unintended and short-interval pregnancies in the United States in general and negative obstetric outcomes specifically associated with COVID-19, access to all effective pregnancy prevention methods during the pandemic was crucial. Objectives: To investigate changes in contraception utilization rates prior to delivery discharge, at outpatient postpartum visits, and at 10 weeks' postpartum, at the largest healthcare system in Central Massachusetts, during the first wave of the COVID-19 pandemic (15 March to 15 May 2020), compared to the same period in 2019. Design: Retrospective cohort review. Methods: Compared perinatal individuals (n = 495) who received prenatal care and delivered at UMass Memorial Medical Center from mid-March to mid-May in both 2019 (non-pandemic) and 2020 (COVID-19 pandemic). Receipt of contraception prior to delivery discharge and at outpatient postpartum visit was estimated and compared between the two time periods using the Chi-square test for categorical variables (or Fisher's exact test when cell counts were < 5) and Student's t-test for continuous variables. Multivariable logistic regression was performed to adjust for confounders. Results: The proportion of individuals who used long-acting reversible contraception before delivery discharge was 4% in 2019 and 13% in 2020 (p = 0.01). Modes of outpatient postpartum visit contraception did not vary from 2019 to 2020, (p = 0.06). Overall, there were no differences in contraception utilization rates at 10 weeks' postpartum from 2019 to 2020, (p = 0.50). Conclusion: Compared to a year prior, immediate postpartum long-acting reversible contraception use increased during the first wave of the COVID-19 pandemic, while overall contraception use at 10 weeks' postpartum remained unchanged. The evaluation of contraceptive use during the most restrictive time of COVID-19 pandemic can help identify opportunities to increase access to effective contraception, such as the immediate postpartum period prior to hospital discharge.

Acute esophageal necrosis may be a potential complication of Coronavirus Disease 2019 (COVID-19). COVID-19 has been associated with a variety of sequelae, including acute respiratory distress syndrome, myocarditis, and thromboembolic events. Here, we present a case of a 43-year-old male who was admitted for acute necrotizing pancreatitis and found to have COVID-19 pneumonia. He subsequently developed acute esophageal necrosis requiring a total esophagectomy. Currently, there are at least five other reported cases of esophageal necrosis with concomitant COVID-19 infection. This case is the first requiring esophagectomy. Future studies may establish esophageal necrosis as a known complication of COVID-19.

Background: Staff shortage is a long-standing issue in long term care facilities (LTCFs) that worsened with the COVID-19 outbreak. Different states in the US have employed various tools to alleviate this issue in LTCFs. We describe the actions taken by the Commonwealth of Massachusetts to assist LTCFs in addressing the staff shortage issue and their outcomes. Therefore, the main question of this study is how to create a central mechanism to allocate severely limited medical staff to healthcare centers during emergencies. Methods: For the Commonwealth of Massachusetts, we developed a mathematical programming model to match severely limited available staff with LTCF demand requests submitted through a designed portal. To find feasible matches and prioritize facility needs, we incorporated restrictions and preferences for both sides. For staff, we considered maximum mileage they are willing to travel, available by date, and short- or long-term work preferences. For LTCFs, we considered their demand quantities for different positions and the level of urgency for their demand. As a secondary goal of this study, by using the feedback entries data received from the LTCFs on their matches, we developed statistical models to determine the most salient features that induced the LTCFs to submit feedback. Results: We used the developed portal to complete about 150 matching sessions in 14 months to match staff to LTCFs in Massachusetts. LTCFs provided feedback for 2,542 matches including 2,064 intentions to hire the matched staff during this time. Further analysis indicated that nursing homes and facilities that entered higher levels of demand to the portal were more likely to provide feedback on the matches and facilities that were prioritized in the matching process due to whole facility testing or low staffing levels were less likely to do so. On the staffing side, matches that involved more experienced staff and staff who can work afternoons, evenings, and overnight were more likely to generate feedback from the facility that they were matched to. Conclusion: Developing a central matching framework to match medical staff to LTCFs at the time of a public health emergency could be an efficient tool for responding to staffing shortages. Such central approaches that help allocate a severely limited resource efficiently during a public emergency can be developed and used for different resource types, as well as provide crucial demand and supply information in different regions and/or demographics.

Objectives: COVID-19 vaccines are widely available, but uptake is suboptimal. To develop strategies to increase vaccination rates, we sought to (1) characterize adults initially hesitant to be vaccinated for COVID-19 who later received the vaccine and (2) identify factors associated with their vaccination decision. Methods: In January 2021, we conducted an online survey of US adults via Prolific that assessed vaccination intent, COVID-19-related knowledge and attitudes, and demographic characteristics. In May 2021, we recontacted respondents to assess vaccination status and factors influencing their vaccination decision. We used χ2 statistics and t tests to examine associations between respondents' vaccination status and their characteristics, knowledge, and attitudes. We analyzed reasons for vaccination using thematic analysis. Results: Of 756 initially vaccine-hesitant respondents, 529 (70.0%) completed the follow-up survey. Nearly half of those initially not sure about vaccination (47.3%, 112 of 237) were vaccinated at follow-up, while 21.2% (62 of 292) of those initially planning not to be vaccinated were vaccinated at follow-up. Of those initially not sure, higher educational attainment, greater knowledge of COVID-19, and a doctor's recommendation were associated with vaccination. Of those initially intending not to be vaccinated, male sex, Democratic political affiliation, receipt of an influenza shot within 5 years, being more worried about COVID-19, and having greater COVID-19 knowledge were associated with increased likelihood of being vaccinated. Of 167 respondents who gave reasons for vaccination, protecting oneself and others (59.9%), practical issues (29.9%), social influences (17.4%), and vaccine safety (13.8%) were the main reasons. Conclusion: Providing information on the protective value of vaccination, implementing rules that make remaining unvaccinated burdensome, making vaccination easy, and providing social support may influence vaccine-hesitant adults to accept vaccination.

The world has finally emerged from the great medical, economic, and social calamity of 2020 to 2022, the COVID-19 pandemic. This Compendium of 10 articles describes various aspects of the effects of SARS-CoV-2 on the cardiovascular system, focusing on the heart. The Minotaur from Greek mythology is an apt metaphor, because this half bull/half man spike-adorned gain of function mutant slaughtered the innocent was nearly impossible to eradicate in his labyrinthian environs, inspired mass fear of the unknown, and ultimately was eliminated by resourceful, determined collaborators.1 Although SARS-CoV-2 infection has not been eliminated, it has been contained to the point of acquiring the status of a manageable infectious disease.

SARS-CoV and SARS-CoV-2 cell entry begins when spike glycoprotein (S) docks with the human ACE2 (hACE2) receptor. While the two coronaviruses share a common receptor and architecture of S, they exhibit differences in interactions with hACE2 as well as differences in proteolytic processing of S that trigger the fusion machine. Understanding how those differences impact S activation is key to understand its function and viral pathogenesis. Here, we investigate hACE2-induced activation in SARS-CoV and SARS-CoV-2 S using hydrogen/deuterium-exchange mass spectrometry (HDX-MS). HDX-MS revealed differences in dynamics in unbound S, including open/closed conformational switching and D614G-induced S stability. Upon hACE2 binding, notable differences in transduction of allosteric changes were observed extending from the receptor binding domain to regions proximal to proteolytic cleavage sites and the fusion peptide. Furthermore, we report that dimeric hACE2, the native oligomeric form of the receptor, does not lead to any more pronounced structural effect in S compared to saturated monomeric hACE2 binding. These experiments provide mechanistic insights into receptor-induced activation of Sarbecovirus spike proteins.

The SARS-CoV2 pandemic has had a profound and lasting impact on healthcare delivery. Gastrointestinal endoscopy services were limited during the early phases of the pandemic, which has resulted in ongoing procedural backlog. Procedural delays have had continuing effects including delayed colorectal cancer (CRC) diagnoses and exacerbation of existing disparities in the CRC-screening and treatment pathways. In this review, we outline these effects as well as the variety of strategies that have been proposed to eliminate this backlog, including increased endoscopy hours, re-triaging of referrals, and alternative CRC-screening strategies.